Highly selective azadipeptide nitrile inhibitors for cathepsin K: design, synthesis and activity assays.
Highly selective azadipeptide nitrile inhibitors for cathepsin K: design, synthesis and activity assays.
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DOI：
10.1039/c2ob26624e
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发表时间：
2013-01
影响因子：
3.2
通讯作者：
Xing-Feng Ren;Hongwei Li;Xuexun Fang;Yuqing Wu;Lincong Wang;Shuxue Zou
中科院分区：
文献类型：
--
作者：
Xing-Feng Ren;Hongwei Li;Xuexun Fang;Yuqing Wu;Lincong Wang;Shuxue Zou
我们已经开发了一系列具有不同P3基团的氮杂二肽腈。三芳基间苯基衍生物化合物13不仅是组织蛋白酶K的有效抑制剂（K（i）= 0.0031 nM），而且对组织蛋白酶B和S具有高度选择性（~1000倍）。对该系列进行的蛋白质-配体对接研究提供了一个可能的解释，为什么化合物13可能比其他化合物，特别是同一系列中的化合物12更有效。
We have developed a series of azadipeptide nitriles with different P3 groups. A triaryl meta-phenyl derivative, compound 13, was not only a potent inhibitor for cathepsin K (K(i) = 0.0031 nM), but also highly selective over both cathepsins B and S (~1000-fold). A protein-ligand docking study performed on the series provided a possible explanation why compound 13 could be significantly more potent than the others, especially compound 12 in the same series.